Preliminary studies show that malarial circumsporozoites bind selectively to heparan sulfate proteoglycans and use these receptors to infect hepatocytes. Our working hypothesis is that the strong interaction between region II-plus peptides of the circumsporozoite protein and hepatocyte heparan sulfate proteoglycans requires a defined oligosaccharide sequence in the heparan sulfate chains. Our approach to identify this sequence involves (i) competition experiments with modified heparinoids with chemically defined alterations, and (ii) characterization of the proportion, size and disaccharide composition of heparan sulfate oligosaccharides that bind to CS protein/peptides.